Placebo-controlled study of the D-4/5-HT2A antagonist fananserin in the treatment of schizophrenia

Objective: The authors' objective was to assess the potential efficacy of f ananserin (RP62203), a potent antagonist at the D-4 and serotonin(2A) (5-HT 2A) receptors, on symptoms of schizophrenia. Method: A double-blind, placeb o-controlled study was conducted in 97 patients. Doses of fananserin reache d 250 mg b.i.d, over 28 days, starting with an 8-day escalation. Most of th e patients were men with paranoid schizophrenia; they were approximately 38 years old. The primary outcome measure was the total Positive and Negative Syndrome Scale score. The patients' mean score on the Positive and Negativ e Syndrome Scale at entry was 91.8 (SD=16.5). A low dropout rate was observ ed in both groups of patients (19 [30%] of those given fananserin and nine [27%] of those given placebo). Results: The total Positive and Negative Syn drome Scale score of the patients given fananserin decreased at endpoint by a mean of 4.2 points (SD=15.4); the score of the patients given placebo de creased by 6.7 points (SD=19.6). No differences between treatments were fou nd on secondary measures such as the Clinical Global impression, Positive a nd Negative Syndrome Scale subscores or individual items, and Brief Psychia tric Rating Scale total score. The patients' extrapyramidal symptoms did no t worsen during the trial, but the patients given fananserin had an increas e in akathisia. The safety profile was good in both groups of patients. Con clusions: The results of this study do not support the prediction that a se lective D-4 antagonist associated with strong 5-HT2A antagonism will exhibi t an antipsychotic effect.